Modulation of human corticospinal excitability by paired associative stimulation in patients with amyotrophic lateral sclerosis and effects of Riluzole

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes an impairment in both the upper and lower motor neurons. The recent description of numerous non-motor signs points to an involvement of the neocortex networks that is more complex than was previously believed. Paired associative stimulation (PAS), a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation, can enhance motor output in the contralateral hand through an NMDA-mediated sensorimotor mechanism. OBJECTIVE To describe the effects of PAS on ALS patients before and after Riluzole intake compared with healthy subjects. METHODS PAS was used to detect differences between 24 newly-diagnosed ALS patients and 25 age-matched healthy controls. MEP amplitude from the abductor pollicis brevis was considered before PAS, immediately after (T0) and after 10 (T10), 20 (T20), 30 (T30) and 60 (T60) minutes. Statistical significance was calculated using RM-ANOVA. RESULTS In healthy controls, PAS significantly increased MEP amplitude at T10, T20 and T30 (p < 0.05). In ALS patients, a significant increase in MEP amplitude was also observed after 60 min (p < 0.05), thus demonstrating NMDA-mediated enhanced facilitatory plasticity. After two weeks of riluzole intake, no MEP amplitude increase was evident after PAS at any time point. In three monomelic-onset ALS patients, sensorimotor facilitation was evident only in the hemisphere corresponding to the affected side and appeared in the opposite hemisphere when the patients manifested contralateral symptoms. CONCLUSIONS PAS may be considered a useful tool when investigating NMDA-mediated neocortical networks in ALS patients and the modulation of such networks after anti-glutamatergic drug intake

Vector field theories in cosmology

Recently proposed theories based on the cosmic presence of a vectorial field are compared and contrasted. In particular the so called Einstein aether theory is discussed in parallel with a recent proposal of a strained space-time theory (Cosmic Defect theory). We show that the latter fits reasonably well the cosmic observed data with only one, or at most two, adjustable parameters, whilst other vector theories use much more. The Newtonian limits are also compared. Finally we show that the CD theory may be considered as a special case of the aether theories, corresponding to a more compact and consistent paradigm.Comment: 19 pages, 1 figure, to appear on Phys. Rev.

Viscoelasticity and Stokes-Einstein relation in repulsive and attractive colloidal glasses

We report a numerical investigation of the visco-elastic behavior in models for steric repulsive and short-range attractive colloidal suspensions, along different paths in the attraction-strength vs packing fraction plane. More specifically, we study the behavior of the viscosity (and its frequency dependence) on approaching the repulsive glass, the attractive glass and in the re-entrant region where viscosity shows a non monotonic behavior on increasing attraction strength. On approaching the glass lines, the increase of the viscosity is consistent with a power-law divergence with the same exponent and critical packing fraction previously obtained for the divergence of the density fluctuations. Based on mode-coupling calculations, we associate the increase of the viscosity with specific contributions from different length scales. We also show that the results are independent on the microscopic dynamics by comparing newtonian and brownian simulations for the same model. Finally we evaluate the Stokes-Einstein relation approaching both glass transitions, finding a clear breakdown which is particularly strong for the case of the attractive glass.Comment: 12 pages; sent to J. Chem. Phy

Looking for the right balance between human and economic costs during COVID-19 outbreak

Since the beginning of Coronavirus 2019 (COVID-19) disease outbreak, there has been a heated debate about public health measures, as they can presumably reduce human costs in the short term but can negatively impact economies and well-being over a longer period. Materials and methods: To study the relationship between health and economic impact of COVID-19, we conducted a secondary research on Italian regions, combining official data (mortality due to COVID-19 and contractions in value added of production for a month of lockdown). Then, we added the tertiles of the number of people tested for COVID-19 and those of health aids to evaluate the correspondence with the outcome measures. Results: Five regions out of 20, the most industrialized northern regions, which were affected both earlier and more severely by the outbreak, registered both mortality and economic value loss above the overall medians. The southern regions, which were affected later and less severely, had low mortality and less economic impact. Conclusions: Our analysis shows that considering health and economic outcomes in the assessment of response to pandemics offers a bigger picture perspective of the outbreak and could allow policymakers and health managers to choose systemic, 'personalized' strategies, in case of a feared second epidemic wave

A computational approach for the discovery of protein–RNA networks

Protein–RNA interactions play important roles in a wide variety of cellular processes, ranging from transcriptional and posttranscriptional regulation of genes to host defense against pathogens. In this chapter we present the computational approach catRAPID to predict protein–RNA interactions and discuss how it could be used to find trends in ribonucleoprotein networks. We envisage that the combination of computational and experimental approaches will be crucial to unravel the role of coding and noncoding RNAs in protein networks

Atrioventricular canal defect and genetic syndromes: the unifying role of sonic hedgehog

The atrioventricular canal defect (AVCD) is a congenital heart defect (CHD) frequently associated with extracardiac anomalies (75%). Previous observations from a personal series of patients with AVCD and "polydactyly syndromes" showed that the distinct morphology and combination of AVCD features in some of these syndromes is reminiscent of the cardiac phenotype found in heterotaxy, a malformation complex previously associated with functional cilia abnormalities and aberrant Hedgehog (Hh) signaling. Hh signaling coordinates multiple aspects of left-right lateralization and cardiovascular growth. Being active at the venous pole the secondary heart field (SHF) is essential for normal development of dorsal mesenchymal protrusion and AVCD formation and septation. Experimental data show that perturbations of different components of the Hh pathway can lead to developmental errors presenting with partially overlapping manifestations and AVCD as a common denominator. We review the potential role of Hh signaling in the pathogenesis of AVCD in different genetic disorders. AVCD can be viewed as part of a "developmental field," according to the concept that malformations can be due to defects in signal transduction cascades or pathways, as morphogenetic units which may be altered by Mendelian mutations, aneuploidies, and environmental causes

Quality of life and psychological impact in patients with atopic dermatitis

Atopic dermatitis (AD) is a dermatological disorder that affects patients' mental health and psychological state in complex ways. The importance of understanding the entire scope of this burden is well recognized, but there is limited comprehensive information about the resulting stress on adult patients with AD. This study aimed to determine the degree of psychological stress in patients with AD compared to healthy participants. A total of 352 adult patients participated in this cross-sectional study-174 with AD and 178 healthy participants. Demographic and clinical data were collected. Itch and sleep disturbance were assessed using a numeric rating scale and a visual analogue scale. The 20-item Toronto Alexithymia Scale (TAS-20) and Beck Depression Inventory (BDI) questionnaires were administered to assess the symptoms of alexithymia and depression. Quality of life (QOL) was assessed in AD patients using the Dermatology Quality Index. In our study, we found high TAS-20 and BDI scores among patients with AD. The prevalence of alexithymic personality features was 56.3% in patients with AD versus 21.3% in healthy controls (p &lt; 0.001). Based on BDI scoring (BDI-21 &gt; 13), depression was suspected in a significantly higher number of patients with AD than in the control group (56.9% (99/174) vs. 15.7% (28/178); p &lt; 0.0001). Eczema Area and Severity Index (EASI) score did not show any significant correlations with psychological parameters. Among clinical parameters, only sleep disturbance was positively correlated with depression (R = 0.307, p &lt; 0.005). Our data show that the severity index score as a representative factor of skin involvement has a limited role in predicting the effect of skin diseases on mental status. Screening and assessment for psychiatric disorders, QOL, and sleep disturbance in patients with atopic dermatitis cannot be neglected by physicians and they should be treated in clinical practice with the consideration of psychosomatic approaches

A post-Keplerian parameter to test gravito-magnetic effects in binary pulsar systems

We study the pulsar timing, focusing on the time delay induced by the gravitational field of the binary systems. In particular, we study the gravito-magnetic correction to the Shapiro time delay in terms of Keplerian and post-Keplerian parameters, and we introduce a new post-Keplerian parameter which is related to the intrinsic angular momentum of the stars. Furthermore, we evaluate the magnitude of these effects for the binary pulsar systems known so far. The expected magnitude is indeed small, but the effect is important per se.Comment: 6 pages, RevTeX, 1 eps figure, accepted for publication in Physical Review D; references adde

An analytical treatment of the Clock Paradox in the framework of the Special and General Theories of Relativity

In this paper we treat the so called clock paradox in an analytical way by assuming that a constant and uniform force F of finite magnitude acts continuously on the moving clock along the direction of its motion assumed to be rectilinear. No inertial motion steps are considered. The rest clock is denoted as (1), the to-and-fro moving clock is (2), the inertial frame in which (1) is at rest in its origin and (2) is seen moving is I and, finally, the accelerated frame in which (2) is at rest in its origin and (1) moves forward and backward is A. We deal with the following questions: I) What is the effect of the finite force acting on (2) on the proper time intervals measured by the two clocks when they reunite? Does a differential aging between the two clocks occur, as it happens when inertial motion and infinite values of the accelerating force is considered? The Special Theory of Relativity is used in order to describe the hyperbolic motion of (2) in the frame I II) Is this effect an absolute one, i.e. does the accelerated observer A comoving with (2) obtain the same results as that in I, both qualitatively and quantitatively, as it is expected? We use the General Theory of Relativity in order to answer this question.Comment: LaTex2e, 19 pages, no tables, no figures. Rewritten version, it amends the previous one whose results about the treatment with General Relativity were wrong. References added. Eq. (55) corrected. More refined version. Comments and suggestions are warmly welcom